Cell cycle progression in eukaryotes is governed via the activities of the cyclin dependent kinases of CDKs. These protein kinases carry out key phosphorylation events thought to be required for passage through all major cell cycle transitions. This program project seeks to analyze the cell cycle from the vantage point of CDK regulation. Components of the program are directed toward elucidation of the mechanisms governing CDK activation as well as identification and characterization of downstream targets. These studies will be carried out using the powerful genetic approaches available in both the budding yeast and fission yeast as well as new molecular genetic approaches for conditional expression and inactivation of genes in animal cells. Two of the components focus primarily on the regulation of the G1/S transition. These involve the study of G1 cyclin gene expression and function as well as the regulation and targets of the CDKs. The remaining two components address the regulation of mitosis both at the level of activation of the M phase specific forms of CDK and at the level of M phase specific CDK targets. The program as a whole is designed as a vehicle for material and intellectual synergism between the component projects. Together these research groups provide diverse expertise and interests directed toward a common problem.